Title: Pre-, pro-, and symbiotics
Key words: prebiotic, probiotic, symbiotic, functional foods, microbial, dysbiosis, gastrointestinal disorders, hypochlorhydria, lactose intolerance, gastroenteritis, endocrine, exocrine, leaky gut, mucosal damage, malabsorption, inflammation, inflammatory bowel disease, liver toxicity, bacteria, bifidobacteria, fructo-oligosaccharides, lactic acid, bacilli, enteric infections, antibiotic, diarrhoes, Helicobacter pylori, pouchitis, dietary fibre, vegetables, calcium, absorption, colocytes, colonic crypts, cardiovascular disease, high density lipoproteins, low density lipoproteins, LDL, HDL, bile acids, deconjugation, serum cholesterol, large bowel, small intestine, lactobacillus, inulin,
Date: Sept 2006
Author: Morgan, G
Pre-, pro-, and symbiotics
Research into the health benefits of prebiotics, probiotics and symbiotics is ongoing, impacting on both clinical practice and the commercialisation of food products. This review will look at the function and the present and future role of these three forms of ‘functional foods’.
Most research in this field has focused on the role of probiotics. As defined by Fuller (Fuller 1989), a probiotic can be defined as “a live microbial food supplement that beneficially affects the host animal by improving its intestinal microbial balance”. This definition highlights the fact that many gastrointestinal disorders are associated with abnormalities in bowel microbial composition, or dysbiosis, with deleterious effects to health. Dysbiosis may be acute, as with gastroenteritis, or chronic, and associated with dietary eating patterns, hypochlorhydria, lactose intolerance and endocrine and exocrine disturbances of the gastrointestinal tract. The damaging effects may be local, in terms of mucosal damage, ‘leaky gut’, maldigestion, malabsorption, inflammation, the degenerative changes associated with inflammatory bowel disease or cancer, or generalised and associated with liver toxicity, immunological impairment, or disturbed metabolism and lipid profiles.
Prebiotics have been defined as “a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth, activity, or both of one or a limited number of bacterial species already resident in the colon” (Gibson 1995). This definition highlights the fact that prebiotics act as food substrates for a restricted spectrum of beneficial bacteria to the detriment of less beneficial bacteria and that this activity is restricted to the large bowel. By definition they are beneficial by promoting the growth of bacteria which are not species specific and may in fact be non-genus specific.
Symbiotics are combinations of pre- and probiotics. Their prebiotic component is designed to synergistically promote the growth of their active probiotic. Some evidence exists that they are able to realise this objective. The differences in the origin, function and efficacy of these three forms of functional foods is illustrated by the following three areas of clinical research.
Abnormalities in the bacterial flora have been shown to occur through both dietary manipulation and as a result of gut pathology. In infancy bottle feeding is associated with lower levels of lactic acid producing bacilli in the gut, particularly Bifidobacteria (Yoshita 1991). In Crohn’s disease a similar dysbiotic picture is seen (Sartor 1999). Prebiotics such as fructo-oligosaccharides have been shown to restore a Bifidobacteria-rich flora in such dysbiotic states (Gibson 1995, Buddington 1996). Supplementation with Bifidobacterium probiotics is also effective. In one trial, combining both in the form of a symbiotic appeared to have a potentiating effect (Roberfroid 1998).
Supplementation trials with probiotics have been shown to help the recolonisation of the gut with friendly bacteria during the course of enteric infections, promoting resolution of the diarrhoea (Alan 1983, Gonzalez 1995, Saavedra 1995). Trials with prebiotics and symbiotics have not been carried out. Similar results have been achieved in ameliorating or preventing antibiotic associated diarrhoea (Siitonen 1990). Several trials, for example, have confirmed the ability of probiotics to reduce the incidence of antibiotic- associated diarrhoea associated with Helicobacter eradication programmes (Armuzzi 2001, Sheu 2002) . One study showed a direct suppression of Helicobacter (Lambert 1996).
Finally, one form of blind-loop syndrome which is of increasing concern is that of pouchitis. Pouchitis is a consequence of dysbiosis resulting from ileo-rectal anastamosis. It is a not uncommon complication of reconstructive bowel surgery for colorectal carcinoma, frequently necessitating an ileostomy revision. Encouraging results have been achieved in treating this condition with both probiotics and symbiotics (Rembacken 1999, Gionchetti 2000, Friedman 2000).
The beneficial effects of dietary fibre and vegetables in preventing colorectal cancer have been well reported (EPIC 2003). The effect may be mediated through oligosaccharides promoting a more normal bowel flora and by encouraging a more rapid transit time through the gut (Roberfroid 1998). Improved calcium absorption and utilisation is also a factor (Gibson 1995, Coudray 1997). Much evidence has now accumulated in rats on the beneficial effects of pre- and probiotics in preventing or reversing the proliferation of colonocytes in colonic crypts underlying the pathogenesis of this disease. Symbiotic combinations appear to be more effective that their isolated pre- and probiotics (Goldin 1996, Rowland 1998, Gallaher 1999). The effect may be mediated through the immuno-modulatory action of probiotics (Isolauri 1995, Gill 1998). Human trials are called for to confirm the results of this animal work.
Trials have mostly focussed on the use of probiotics and symbiotics in this area. Review of the literature indicates a lowering of cholesterol and LDL by these agents (Taylor 1998, Anderson 1999, Kiessling 2002). Their precise mode of action is not known, but it is known that they do lead to deconjugation of bile acids which helps to lower cholesterol levels (Gilliland 1977). For each 1% lowering of serum cholesterol it has been calculated there is a 2-3% reduction in the rate of cardiovascular disease with a potential 10% reduction in cardiovascular disease (McNaught 2001, Kiessling 2002).
Associated elevations in HDL (Mikes 1995, Kiessling 2002) and the production of a more normal LDL/HDL ratio indicate a role for such supplements but large prospective studies are needed to confirm this. One study indicated a synergistic effect of the prebiotic fructooligosaccharide with a probiotic in further reducing LDL levels (Schaafsma 1998). No trials have been done so far looking at the effect of prebiotics alone.
To date, research within the field of prebiotics and probiotics has been concerned with the identification of bacterial strains with increased selectivity and potency. The development of sophisticated techniques for sequencing bacterial genomes using 16S rRNA and fluorescent-light emission technology has made this whole process far more refined and precise (Langendijk 1995, Chalfie 1994). Issues regarding viability and therapeutic efficacy remain however.
Unlike prebiotics which are able to withstand processing, cooking, and transit through the stomach and small intestine to the large bowel, probiotics are fragile organisms that need to be stored in controlled conditions. On entering the stomach they need to be able to withstand a low pH and competitive inhibition in the gastrointestinal tract, where they are required to become adherent to the mucosa prior to multiplying and establishing a new bowel flora equilibrium. Certain favourable laboratory strains may in practice be unable to reach their target in order to realise their potential, as, for example, one lactobacillus strain with high beta-glucuronidase activity and mucosal adhesiveness in the laboratory which would theoretically have been useful in the treatment of lactose deficiency. In practice it was found to be able to pass into the large bowel but not to establish itself in the small intestine where it could exert its purposed clinical effect (Saltzman 1999).
Other bacterial strains, on the other hand, are able to fulfil their clinical role, as for example is the case with certain lactobacillus strains in the treatment of pouchitis (Gionchetti 2000, Friedman 2000). Further research and developmental work is needed to isolate the most beneficial probiotics for the treatment of specific medical conditions. In addition the viability of commercial pro- and synbiotics needs further reappraisal as most if not all commercial Lactobacilli and Bifidobacteria containing yogurts appear to be non-viable (Gilliland 1997, Kailasapathy 2000). New strains such as Lactobacillus GG may help to overcome this problem (Sheu 2002).
Due to their utility and ease of manufacture, prebiotic use in the food industry will continue to grow. The benefical effects of inulin-containing foods and supplements has been widely promoted. Their addition to formula baby feeds would be one area where their use would be medically beneficial, through helping to promote Bifidobacteria growth. Their use in probiotic supplements is already widespread and is to be welcomed. Research within this area, however, does not match that carried out within the field of probiotics.
It remains to be determined whether more specific prebiotics can be developed which can be tailored to meet the metabolic needs of specific strains of favourable bacteria. This would help to further their use both in the form of prebiotics and symbiotics. Although, by definition, prebiotics act as substrates to favourable bacteria, this development would undoubtedly add refinements which would be of especial benefit in the medical field.
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